title: Synthesis and biological activity of new HMG-CoA reductase inhibitors. 1. Lactones of pyridine- and pyrimidine-substituted 3,5-dihydroxy-6-heptenoic (-heptanoic) acids.
abstract: Lactones of pyridine- and pyrimidine-substituted 3,5-dihydroxy-6-heptenoic (-heptanoic) acids 2-4 have been synthesized. Extensive exploration of structure-activity relationships led to several compounds exceeding the inhibitory activity of mevinolin (1b) on HMG-CoA reductase, both in vitro and in vivo. First clinical trials with 2i (HR 780) are in preparation.
authors.affiliation: Hoechst AG, Frankfurt/M, West Germany.
authors.forename: G
authors.initials: G
authors.lastname: Beck
authors.forename: K
authors.initials: K
authors.lastname: Kesseler
authors.forename: E
authors.initials: E
authors.lastname: Baader
authors.forename: W
authors.initials: W
authors.lastname: Bartmann
authors.forename: A
authors.initials: A
authors.lastname: Bergmann
authors.forename: E
authors.initials: E
authors.lastname: Granzer
authors.forename: H
authors.initials: H
authors.lastname: Jendralla
authors.forename: B
authors.initials: B
authors.lastname: von Kerekjarto
authors.forename: R
authors.initials: R
authors.lastname: Krause
authors.forename: E
authors.initials: E
authors.lastname: Paulus
mesh_terms: D000085:Acetates / Q000378:metabolism; D000818:Animals; D000924:Anticholesteremic Agents; D055598:Chemical Phenomena; D002621:Chemistry; D002784:Cholesterol / Q000096:biosynthesis / Q000097:blood; D006538:Heptanoic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007783:Lactones / Q000138:chemical synthesis / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D008297:Male; D008968:Molecular Conformation; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014961:X-Ray Diffraction
chemical_list: D000085:Acetates; D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007783:Lactones; D011725:Pyridines; D011743:Pyrimidines; C062437:HR 780; D002784:Cholesterol